2,3,4-Trifluoro-5-(iodo or bromo)benzoic acid is useful as a synthetic intermediate of drugs, agricultural chemicals and the like, and it is used as, for example, an important intermediate for production of the diphenylamines described in Patent document 1, which are particularly useful as anticancer agents.
2,3,4-Trifluoro-5-bromobenzoic acid is useful as, for example, a raw material for production of 5-bromo-3,4-difluoro-2-(4-iodo-2-methylphenylamino)benzoic acid, an important intermediate, and it can be converted to 5-bromo-3,4-difluoro-2-(4-iodo-2-methylphenylamino)benzoic acid by coupling with 2-amino-5-iodotoluene by reference to the method described in Patent document 1. 5-Bromo-3,4-difluoro-2-(4-iodo-2-methylphenylamino)benzoic acid can be converted to a phenylaminobenzhydroxamic acid derivative that is an anticancer agent by reference to the method described in Patent document 1.
On the other hand, 2,3,4-trifluoro-5-iodobenzoic acid is also useful as a raw material for production of 2,3,4-trifluoro-5-trifluoromethylbenzoic acid, which is an important intermediate in the synthesis of quinolone carboxylic acids that are useful as antimicrobial agents or antiviral agents. 2,3,4-trifluoro-5-trifluoromethylbenzoic acid can be converted to a quinolone carboxylic acid with a 6-trifluoromethyl group by reference to the method described in, for example, Patent document 2 or Patent document 3.
Examples of known processes for obtaining 2,3,4-trifluoro-5-iodobenzoic acid include: (i) a process in which a 2,3,4-trifluorobenzoic acid is used as a starting material and subjected to a multistep reaction (for example, 2,3,4-trifluorobenzoic acid is used as a raw material and subjected to the following three steps: nitration; reduction of the nitro groups to amino groups; and iodination by Sandmeyer reaction (Patent document 4)); and (ii) a process in which 2,3,4-trifluoro-1,5-diiodobenzene is treated with LDA and then reacted with carbon dioxide (Non-patent document 1).
An example of a known process for obtaining 2,3,4-trifluoro-5-bromobenzoic acid is: (iii) a process in which 1-bromo-2,3,4-trifluorobenzene is used as a starting material and subjected to reaction with carbon dioxide at −78° C. in the presence of base for carboxylation (Patent document 1).
Patent document 1: International Patent Publication No. WO 99/01426
Patent document 2: International Patent Publication No. WO 96/02512
Patent document 3: Japanese Patent Application Laid-Open SHO 64-66180
Patent document 4: Japanese Patent Publication No. 3573249
Non-patent document 1: Eur. J. Org. Chem. 2001, 2771-2777